Chalcones Repressed the AURKA and MDR Proteins Involved in Metastasis and Multiple Drug Resistance in Breast Cancer Cell Lines

Komoto, Tatiana Takahasi; Bernardes, Tayná Minervina; Silva, Gabriel; Bitencourt, Tamires Aparecida; Baek, Seung Joon; Marins, Mozart; Fachin, Ana Lúcia

doi:10.3390/molecules23082018

Cited by 30 publications

(22 citation statements)

References 33 publications

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“…The mutation or overexpression of AURKA may also cause carcinogenesis. AURKA is highly expressed in many tumors, such as breast 48 , ovarian 49 , gastric 50 and colon cancers 51 . The abnormal expression of AURKA in various solid tumors is closely related to tumor occurrence and development.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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Aberrant methylated genes (DMGs) play an important role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). In this study, we aimed to integrate three cohorts profile datasets to ascertain aberrant methylated-differentially expressed genes and pathways associated with ESCC by comprehensive bioinformatics analysis. We downloaded data of gene expression microarrays (GSE20347, GSE38129) and gene methylation microarrays (GSE52826) from the Gene Expression Omnibus (GEO) database. Aberrantly differentially expressed genes (DEGs) were obtained by GEO2R tool. The David database was then used to perform Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses on selected genes. STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network, then the modules in the PPI networks were analyzed with MCODE and the hub genes chose from the PPI networks were verified by Oncomine and TCGA database. In total, 291 hypomethylation-high expression genes and 168 hypermethylation-low expression genes were identified at the screening step, and finally found six mostly changed hub genes including KIF14, CDK1, AURKA, LCN2, TGM1, and DSG1. Pathway analysis indicated that aberrantly methylated DEGs mainly associated with the P13K-AKT signaling, cAMP signaling and cell cycle process. After validation in multiple databases, most hub genes remained significant. Patients with high expression of AURKA were associated with shorter overall survival. To summarize, we have identified six feasible aberrant methylated-differentially expressed genes and pathways in ESCC by bioinformatics analysis, potentially providing valuable information for the molecular mechanisms of ESCC. Our data combined the analysis of gene expression profiling microarrays and gene methylation profiling microarrays, simultaneously, and in this way, it can shed a light for screening and diagnosis of ESCC in future. Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, with incidence rates ranking fourth and eighth in China and worldwide, respectively 1,2. ESCC is a serious threat to human health, and its five-year survival rate is less than 10%, making it a leading cause of cancer-related death 3. So far,

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Section: Discussionmentioning

confidence: 99%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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“…Patients with UCC and increased AURKA mRNA expression in tumor tissues not only exhibit high rates of cancer metastasis and high-grade tumors but also have relatively low overall and UCC-specific survival 22. AURKA overexpression also promotes cancer metastasis, increases drug resistance, and is associated with poor prognosis 23-26. In a study on 786 men with oral cancer, patients with the GG genotype and G allele of AURKA rs2064863 were at a 1.365-fold higher risk of stage III or IV oral cancer than were those with the wild-type AA genotype 10.…”

Section: Discussionmentioning

confidence: 99%

Impacts of AURKA Genetic Polymorphism on Urothelial Cell Carcinoma Development

Huang

Chen

et al. 2019

J. Cancer

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Urothelial cell carcinoma (UCC) is the most common primary malignancy of the urinary system and the second-most common type of renal cell carcinoma. Aurora kinase A (AURKA), a serine/threonine kinase, has a critical role in centrosome duplication, spindle assembly checkpoint, and cytokinesis. Here, we determined the correlation between UCC susceptibility and AURKA polymorphisms. We used real-time polymerase chain reaction to compare the genotype distributions and allelic frequencies of four single-nucleotide polymorphisms (SNPs) of AURKA , namely rs1047972, rs2273535, rs2064863, and rs6024836, between 431 UCC cases and 862 healthy controls. Logistic regression models demonstrated that the G allele of rs2064863, a genetic polymorphism of AURKA, exhibited a significant protective effect against UCC among the 862 nonsmokers. Moreover, patients with rs2064863 G allele exhibited a slightly lower risk of lymph node metastasis and those with rs6024836 G allele exhibited a lower risk of distant metastases. Our study suggested that several variants of AURKA SNPs rs2064863 and rs6024836 may serve as critical predictors for the clinical status of UCC.

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“…2′-Hydroxy-2,4,6′-trimethoxychalcone was shown to significantly inhibit the protein expression of P-gp in MES-SA/DX5 cells and overcome P-gp-mediated MDR in drug-resistant uterine sarcoma cells (20). Komoto et al (21) found that the chalcone licochalcone A decreased the protein expression of P-gp in BT20 breast cancer cells. The present study demonstrated that FKA did not block the efflux of Rh-123 out of cells (data not shown), which demonstrated that FKA had no influence on the efflux function of ABC transporters.…”

Section: Discussionmentioning

confidence: 99%

Activity and mechanism of flavokawain A in inhibiting permeability‑glycoprotein expression in paclitaxel resistance of lung cancer

Zheng

et al. 2019

Oncol Lett

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Lung cancer is one of the most common cancers, which is the leading cause of cancer-related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of paclitaxel (PTX)-resistant lung cancer A549 (A549/T) have not been investigated. In the present study, the effect of FKA on the viability of A549/T and hepatotoxicity in normal liver epithelial cells was detected by Cell Counting Kit-8 assay. Flow cytometry, western blot analysis and Annexin V-FITC/PI apoptosis detection kit were used to assess cell apoptosis. The effect of FKA on permeability-glycoprotein (P-gp) expression was measured by reverse transcription-PCR and western blot analysis. The results indicated that FKA dose-dependently inhibited cell proliferation and induced cell apoptosis in PTX-resistant A549/T cells, with an IC50 value of ~21 µM, while the IC50 value of A549/T cells to PTX was 34.64 µM. FKA had no hepatic toxicity in liver epithelial cells. P-gp, which contributes to the chemoresistant phenotype, was not expressed in A549 cells but was remarkably enhanced in A549/T cells. FKA (30 µM) decreased P-gp protein expression at 24 h by 3-fold. Furthermore, FKA downregulated P-gp expression by blocking the PI3K/Akt pathway. These findings suggest FKA as a potential candidate for the treatment of PTX-resistant lung cancer.

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Chalcones Repressed the AURKA and MDR Proteins Involved in Metastasis and Multiple Drug Resistance in Breast Cancer Cell Lines

Cited by 30 publications

References 33 publications

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Impacts of AURKA Genetic Polymorphism on Urothelial Cell Carcinoma Development

Activity and mechanism of flavokawain A in inhibiting permeability‑glycoprotein expression in paclitaxel resistance of lung cancer

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